Nontuberculous Mycobacteria In Cystic Fibrosis Research Articles

Nontuberculous mycobacteria in cystic fibrosis.

Nontuberculous mycobacteria (NTM) are challenging infections among people with cystic fibrosis (pwCF) as the source, modes of transmission, and best practices for diagnosis and treatment are not known. Investigators have defined aspects of NTM infection that are unique to the CF population, as well as features shared with other conditions at risk. This review describes recent advances in our understanding of NTM infection among pwCF. The presence of dominant circulating clones of Mycobacterium abscessus within the CF community worldwide continue to be described, as well as pathogen phenotypes that could evoke greater environmental fitness and infectivity. The risk of direct or indirect transmission between pwCF remains an active focus of investigation, with divergent findings and conclusions reached in a site-specific fashion. Derived largely from studies in non-CF populations, new clinical guidelines are now available. A wide variety of agents are in preclinical development or early phase trials with promising findings, and new therapeutic targets have been identified as our understanding of the complex biology of NTM continues to expand. Significant challenges remain in the fight against NTM, however, recent advances in our understanding of the genetics, epidemiology and pathophysiology of pulmonary NTM infection in pwCF are leading efforts to improve clinical care.

Clinical Pharmacokinetic and Pharmacodynamic Considerations in the Drug Treatment of Non-Tuberculous Mycobacteria in Cystic Fibrosis.

Non-tuberculous mycobacteria (NTM) are an emerging group of pulmonary infectious pathogens of increasing importance to the management of patients with cystic fibrosis (CF). NTM include slow-growing mycobacteria such as Mycobacterium avium complex (MAC) and rapidly growing mycobacteria such as Mycobacterium abscessus. The incidence of NTM in the CF population is increasing and infection contributes to significant morbidity to the patient and costs to the health system. Treating M. abscessus requires the combination of multiple costly antibiotics for months, with potentially significant toxicity associated with treatment. Although international guidelines for the treatment of NTM infection in CF are available, there are a lack of robust pharmacokinetic studies in CF patients to inform dosing and drug choice. This paper aims to outline the pharmacokinetic and pharmacodynamic factors informing the optimal treatment of NTM infections in CF.

Urine lipoarabinomannan as a marker for low-risk of NTM infection in the CF airway

BackgroundIndividuals with Cystic fibrosis (CF) are the most vulnerable population for pulmonary infection with nontuberculous mycobacteria (NTM). Screening, diagnosis, and assessment of treatment response currently depend on traditional culture techniques, but sputum analysis for NTM in CF is challenging, and associated with a low sensitivity. The cell wall lipoarabinomannan (LAM), a lipoglycan found in all mycobacterial species, and has been validated as a biomarker in urine for active Mycobacterium tuberculosis infection. MethodsUrine from a CF cohort (n = 44) well-characterized for NTM infection status by airway cultures was analyzed for LAM by gas chromatography/mass spectrometry. All subjects with positive sputum cultures for NTM had varying amounts of LAM in their urine. No LAM was detected in subjects who never had a positive culture (14/45). One individual initially classified as NTM sputum negative subsequently developed NTM disease 657 days after the initial urine LAM testing. Repeat urine LAM testing turned positive, correlating to her positive NTM status. Subjects infected with subspecies of M. abscessus had greater LAM quantities than those infected with M. avium complex (MAC). There was no correlation with disease activity or treatment status and LAM quantity. A TB Capture ELISA using anti-LAM antibodies demonstrated very poor sensitivity in identifying individuals with positive NTM sputum cultures. ConclusionThese findings support the conclusion that urine LAM related to NTM infection may be a useful screening test to determine patients at low risk for having a positive NTM sputum culture, as part of a lifetime screening strategy in the CF population.

Healthcare-associated Links in Transmission of Nontuberculous Mycobacteria in Cystic Fibrosis

Healthcare-associated Links in Transmission of Nontuberculous Mycobacteria in Cystic Fibrosis

Nontuberculous mycobacteria in cystic fibrosis: Updates and the path forward.

Nontuberculous mycobacteria (NTM) are troublesome pathogens that can cause significant pulmonary disease in patients with cystic fibrosis (CF). Diagnosis can be difficult in the setting of underlying CF and treatment regimens are burdensome on both patients and providers. Recent consensus guidelines for treatment of NTM in CF have provided a guide for the CF community, however research is lagging regarding accuracy of our diagnostic abilities and treatment efficacy. In this review, we provide new insights into the complexity of NTM from emerging whole genome sequencing data, a summary of current NTM diagnosis and treatment guidelines, highlight new treatment options, and discuss future research projects which aim to better define which patients to treat and timing and duration of treatment.

112 Nontuberculous mycobacteria in cystic fibrosis of western Andalusia

112 Nontuberculous mycobacteria in cystic fibrosis of western Andalusia

53 Non-tuberculous mycobacteria in cystic fibrosis: A single centre study of prevalence, sampling and microbiological outcomes

Background The rise in non tuberculous mycobacteria (NTM) from cystic fibrosis patients is of concern. Discerning pathogenicity from colonisation increases difficulty in treatment. Objective The aims of the study were to evaluate the impact of NTM's by calculating prevalence and species distribution. Macrolide use in the context of NTM sampling was analyzed as were microbiological outcomes of patients who received treatment with those not considered for therapy. Methods This was a single centre study of cystic fibrosis patients in Glasgow. Electronic databases and written case notes were used to gain microbiological and clinical information. Data was collected from patients who had at least one NTM screen processed. Results The prevalence of NTMs was 14.9%, the majority species was the Mycobacterium abscessus group (MABSC) followed by Mycobacterium avium complex (MAC). The majority received macrolides prior (58%) and equal figures after first positive culture (50%), predominantly within the MAC group. Despite treatment, microbiological eradication rates (57%) were similar to untreated transient colonisation (61%). Data showed MABSC equally likely to be eradicated or persistent post treatment (50% vs 50%). Conclusion The data showed an increasing prevalence of NTMs with predominance of MABSC. A potential link between macrolide monotherapy and increasing, persisting NTMs is a concern. This requires more research and judicial use of macrolides. The emergence of MABSC highlights that further studies are required regarding subspecies and transmission. These increasing numbers mandate a multidisciplinary approach for management.

Nontuberculous mycobacteria in cystic fibrosis and non-cystic fibrosis bronchiectasis.

Increasing numbers of cystic fibrosis (CF) and non-CF bronchiectasis patients are affected by pulmonary nontuberculous mycobacteria (NTM) infection worldwide. Two species of NTM account for up to 95% of the pulmonary NTM infections: Mycobacterium avium complex (MAC) and Mycobacterium abscessus complex (MABSC). Diagnosis of pulmonary NTM infection is based on criteria specified in the 2007 American Thoracic Society/Infectious Disease Society of America (ATS/IDSA) guidelines. While many initial positive cultures do not progress to active NTM disease, even a single positive NTM sputum culture obtained from higher risk groups such as classic CF or older women with bronchiectasis and very low body mass index should be closely monitored for progressive disease. Macrolides remain the most effective agents available against MAC and MABSC. Infection with MABSC may be associated with worse clinical outcomes, as more than half of MABSC isolates have inducible macrolide resistance conferred by an active erm(41) gene. Of growing concern in CF is that MABSC is becoming more common than MAC, seems to target younger patients with classic CF, and is more difficult to manage, often requiring prolonged courses of intravenous antibiotics. Recurrence rates of NTM after initial successful treatment remain high, likely due to nonmodifiable risk factors raising the question of whether secondary prophylaxis is feasible. More rapid and readily available methods for detecting inducible macrolide resistance and better in vitro susceptibility testing methods for other drugs that correlate with clinical responses are needed. This is crucial to identify more effective regimens of existing drugs and for development of novel drugs for NTM infection.

Nontuberculous mycobacteria

Although patients with cystic fibrosis (CF) face numerous infectious pathogens over the course of their lifespan, increasing attention has recently been paid to nontuberculous mycobacteria (NTM). As reported prevalence rates rise across many countries such as the United States, the ability to recognize disease caused by NTM and subsequently treat such disease has become increasingly important. This review summarizes new observations on the epidemiology of NTM in CF as well as key elements to consider during the treatment phase. Although overall rates of NTM isolation appear to be increasing, particular concern has focused on the emerging predominance of Mycobacterium abscessus. New data suggest that chronic macrolide therapy now part of routine CF care has contributed to this rise; however, these have yet to be confirmed prospectively. Transmission of M. abscessus between CF patients has also now been described through the use of genome sequencing. Although the greater virulence of M. abscessus makes it a challenging species to treat, identification of the subspecies type can now determine the presence of inducible macrolide resistance, thereby helping to guide treatment. Given increasing prevalence rates, clinicians should maintain a high level of suspicion for NTM as disease-causing organisms in CF, particularly for M. abscessus. New knowledge regarding this species, however, can help to tailor appropriate therapy.

Nontuberculous Mycobacteria in Patients with Cystic Fibrosis

As a result of their underlying lung disease, patients with cystic fibrosis (CF) have a higher risk of developing nontuberculous mycobacteria (NTM) infections compared with the general population. Although NTM may be present intermittently in low amounts in the airways of CF patients without an apparent clinical effect, progressive respiratory decline due to NTM disease may also occur. Identifying this latter group of patients can be challenging for clinicians because the usual symptoms exhibited by infected individuals without CF may be difficult to distinguish from the baseline respiratory dysfunction of a patient with CF. The distinction, however, is of utmost importance because those patients with clinical worsening may benefit considerably from antimycobacterial treatment. For CF patients under evaluation for lung transplantation, NTM can play a critical role in determining overall outcomes, and treatment in the pre- and post-transplant period may be vital to success. A general approach to NTM in CF thus involves surveillance to detect NTM, careful monitoring for associated clinical decline, and consideration of treatment given for those with an otherwise unexplained deterioration. In this review, the epidemiology and clinical course of NTM in CF is described with an algorithm for management proposed.

Non-tuberculous mycobacteria in cystic fibrosis

Non-tuberculous mycobacteria (NTM) are environmental organisms found in soil and water throughout the world that can cause chronic lung infection, usually in the context of structural lung disease or immunodeficiency.1 There is considerable evidence that rates of NTM infection are increasing in patients with Cystic Fibrosis (CF).2 In contrast to Mycobacterium tuberculosis, NTM do not seem to be transmissible from person to person nor re-activate following latent infection.3 Observed increases in NTM infection in CF patients are therefore likely to reflect increased exposure and/or increased susceptibility to infection. This review aims to summarize the epidemiology, diagnosis and treatment of NTM infection in CF patients focusing on the two most common mycobacterial groups causing disease: the M. avium-intracellulare complex (MAC) and the M. abscessus complex (MABSC).

Nontuberculous mycobacteria in cystic fibrosis associated with allergic bronchopulmonary aspergillosis and steroid therapy

Nontuberculous mycobacterial (NTM) infection, particularly due to Mycobacterium abscessus, is an emerging disease that can be relentlessly progressive, particularly in cystic fibrosis (CF) patients. The risk factors that were associated with this increasingly symptomatic infection in a group of CF patients were investigated. A total of 139 CF patients aged 2-52 yrs were reviewed. Sputum was cultured for NTM annually or whenever clinical deterioration was unexplained. In total, 12 patients (8.6%) had positive cultures and six (4.3%) met the criteria for NTM pulmonary disease (five with M. abscessus). Five had allergic bronchopulmonary aspergillosis (ABPA) compared with one out of 133 patients without NTM disease. Five had received systemic steroids (four as a treatment for ABPA) compared with only one out of 133 without NTM lung disease. All six NTM patients deteriorated markedly following mycobacterial infection, and forced expiratory volume in one second dropped 18-46%. Despite prolonged triple antibiotic therapy, M. abscessus was not eradicated, and four out of six did not return to baseline clinically. In conclusion, severe nontuberculous mycobacterial lung disease, particularly with Mycobacterium abscessus, is becoming a perplexing challenge in cystic fibrosis patients. Allergic bronchopulmonary aspergillosis and systemic steroids appear to be risk factors, although small patient numbers limit this to a descriptive observation. When pulmonary condition deteriorates, increased surveillance for mycobacteria would enable prompt diagnosis and treatment.

Nontuberculous mycobacteria. I: multicenter prevalence study in cystic fibrosis.

Nontuberculous mycobacteria (NTM) are potential respiratory pathogens in cystic fibrosis (CF). To assess the species-specific prevalence and risk factors for acquisition, we conducted a prospective, cross-sectional study of the prevalence of NTM and clinical features of patients at 21 U.S. centers. Almost 10% of patients with CF who were 10 years or older were included (n = 986). The overall prevalence of NTM in sputum was 13.0% (range by center, 7-24%). Mycobacterium avium complex (72%) and Mycobacterium abscessus (16%) were the most common species. When compared with patients with CF without NTM, culture-positive subjects were older (26 vs. 22 years, p < 0.001), had a higher FEV1 (60 vs. 54%, p < 0.01), higher frequency of Staphylococcus aureus (43 vs. 31%, p < 0.01), and lower frequency of Pseudomonas aeruginosa (71 vs. 82%, p < 0.01). Molecular typing revealed that almost all patients within each center had unique NTM strains. In summary, NTM are common in patients with CF, but neither person-to-person nor nosocomial acquisition explained the high prevalence. Older age was the most significant predictor for isolation of NTM. The clinical significance of NTM in CF is incompletely defined, but patients with these organisms should be monitored with repeat cultures.

Non-tuberculous mycobacteria in cystic fibrosis

BACKGROUNDThe clinical significance of the presence of non-tuberculous mycobacteria in the sputum of patients with cystic fibrosis is unclear. A retrospective case-control study was performed to assess possible risk factors...